Metalloenzymes and Myocardial Infarction

A B S T R A C T Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)f per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested.The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW1 per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N. P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW1 per day) produced positive N, P, Na, and

Section: Resultsmentioning

confidence: 99%

“…Activities of CPK and LDH in fasting serum were measured by the methods of Rosalski (7), and Wacker, Ulmer, and Vallee (8), respectively. In the dystrophy cases, strength of 68 muscles was measured before and upon completion of each course of hormone treatment.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Effects of Human Growth Hormone and of Estrogens in Boys with Duchenne Muscular Dystrophy

Rudman¹,

Chyatte²,

Patterson³

et al. 1972

“…Serum activities of lactic dehydrogenase (LDH), alanine aminotransferase (ALT), alkaline phosphatase (ALP), sorbitol dehydrogenase (SDH), and 5' nucleotidase (5'-NT) and the serum concentration of total bile acids (TBA) were measured according to published procedures (28)(29)(30)(31) …”

Section: Methodsmentioning

confidence: 99%

Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation.

Kadiiska¹,

Burkitt²,

Xiang³

et al. 1995

130

Electron spin resonance (ESR) spectroscopy has been used to investigate hydroxyl radical generation in rats with chronic dietary iron loading. A secondary radical spin-trapping technique was used where hydroxyl radical forms methyl radical upon reaction with DMSO. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap a-phenyl-N-t-butylnitrone (PBN). This adduct was detected in the bile of rats 10 wk after being fed an iron-loading diet and 40 min after the i.p. injection of the spin trap PBN dissolved in DMSO. Bile samples were collected into a solution of the ferrous stabilizing chelator 2,2 '-dipyridyl in order to prevent the generation of radical adducts ex vivo during bile collection. Identification of the ESR spectrum of the major radical adduct as that of PBN/ 'CH3 provides evidence for the generation of the hydroxyl radical during iron supplementation. Desferal completely inhibited in vivo hydroxyl radical generation stimulated by high dietary iron intake. No radical adducts were detected in rats which were fed the control diet for the same period of time. This is the first evidence of hydroxyl radical generation in chronic iron-loaded rats. (J. Clin. Invest. 1995.

“…Release of the cytoplasmic enzyme, lactate dehydrogenase, was monitored on aliquots ofsupernatants after cell incubations and on 0.1 % Triton X-100 extracts of neutrophils by the method ofWacker et al (26), to determine whether neutrophil lysis had occurred during incubations with the agonists.…”

Section: Methodsmentioning

confidence: 99%

Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation.

Wachtfogel

Abrams²,

Kucich³

et al. 1988

We investigated whether adhesive glycoproteins, such as fibronectin or fibrinogen, could function to provide a nidus for neutrophil degranulation. Elastase release in recalcified plasma was normal in afibrinogenemic plasma, but 73% less in plasma depleted of fibronectin. Proteolytic digests of fibronectin, but not intact fibronectin (50-1,000 gg/ml), induced a concentration-dependent release of neutrophil elastase and lactoferrin. MAbs N293, which recognized the mid-molecule of fibronectin, N294, which was directed toward the 11-kD cell adhesive fragment, and N295, generated against the amino terminal of the 11-kD fragment, inhibited the release of elastase by 7, 24, and 60%, respectively. The cytoadhesive tetrapeptide portion of fibronectin, Arg-Gly-Asp-Ser (250-1,000 pg/ml), released 1.94±0.10 jig/ml of elastase from 107 neutrophils, in contrast to the lack of release by the control hexapeptide, Arg-GlyTyr-Ser-Leu-Gly. Plasmin appeared to be the enzyme responsible for fibronectin cleavage, since neutrophil elastase release in plasma that had been depleted of plasminogen was decreased and reconstitution of plasminogen-deficient plasma with purified plasminogen corrected the abnormal release. Plasmin cleaved fibronectin to multiple degradation products, each < 200 kD. This fibronectin digest released 1.05 jig/ml of elastase from 107 neutrophils. We suggest that the activation of plasminogen leads to the formation of fibronectin degradation products capable of functioning as agonists for neutrophils.